The anticancer properties of the nanocomposite of low-nanoscale Ag nanoparticles obtained in SiO2-grafted polyacrylamide carrier.

Abstract

BACKGROUND/AIMS: Silver-based nanomedicine is an ongoing trend in anticancer research. Polymers greatly improve the stability of bare metal silver and improve its interaction with cells. We aimed to evaluate the anticancer efficiency of the synthesized Ag/polymer nanocomposite against B95-8 and Wish cell lines. METHODS: A highly stable low-nanoscale Ag/silica-grafted polyacrylamide nanocomposite (Ag/Hyb) with a mean particle size of 6 nm, estimated by TEM, was obtained. Malignant cell lines: B95-8 (Burkitt lymphoma), Wish (human amniotic with marker chromosomes of HeLa), and the control MDCK cell lines were used. To assess cell viability, the MTT test was applied. To find putative targets of Ag/Hyb, mitochondrial respiration, lipid peroxidation, and NO synthase activity were evaluated in rat tissue homogenates. RESULTS: The half-inhibition (IC50) of B95-8 and Wish cells viability was 6.1 and 7.8 µg/ml, respectively, and was not reached in the control MDCK cells, which indicated high anticancer activity. At the same dilutions, the matrix was similarly toxic to B95-8 cells but safe to Wish and MDCK cells. Dose-dependent suppression of glutamate-driven respiration, strong NO synthases (NOS) stimulation, and the reduction of lipid peroxidation (LPO) within the same concentration range were observed. The correlation was found between NOS activation and mitochondrial CI suppression, which indicated possible involvement of these processes in cytotoxicity mechanisms of Ag/Hyb. CONCLUSIONS: A low-nanoscale Ag/SiO2-g-PAAm nanocomposite with high anticancer activity in vitro in a low micromolar concentration range was obtained. The putative mechanism of Ag/Hyb action was proposed, in which Complex I and NOS activity could be involved in anticancer effects. Based on the experiments, we came to the conclusion that Ag/Hyb is a promising system for the future design of anticancer preparations; however, molecular mechanisms of Ag/Hyb action in different cancer cell types require detailed study in the future.